Safety and efficacy of various dosages of ocrelizumab in Japanese patients with rheumatoid arthritis with an inadequate response to methotrexate therapy: A placebo-controlled double-blind parallel-group study

Masayoshi Harigai, Yoshiya Tanaka, Shingo Maisawa, Kazuhide Tanimura, Hiroki Takahashi, Yukitomo Urata, Yasuhiko Hirabayashi, Tomonori Ishii, Hiroshi Fujii, Takayuki Sumida, Chihiro Terai, Ryutaro Matsumura, Makoto Sueishi, Kazuhiko Yamamoto, Akio Yamada, Daitaro Kurosaka, Akio Mimori, Yusuke Miwa, Masataka Kuwana, Shinichi KawaiYoshiaki Ishigatsubo, Kazunori Sugimoto, Noriyoshi Ogawa, Toshiaki Miyamoto, Shigenori Tamaki, Motokazu Kai, Daisuke Kawabata, Toshio Tanaka, Masaaki Inaba, Shunichi Kumagai, Akio Morinobu, Yasushi Miura, Hajime Sano, Naoki Kashihara, Yoshitaka Morita, Kazuhiko Ezawa, Yuji Yamanishi, Masanori Kawashima, Seizo Yamana, Mitsuhiro Iwahashi, Hiroaki Dobashi, Kiyoshi Takasugi, Takahiko Horiuchi, Eiichi Suematsu, Takaaki Fukuda, Katsumi Eguchi, Atsushi Kawakami

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective. To evaluate the safety and efficacy of ocrelizumab (OCR) in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Methods. RA patients with an inadequate response to MTX 6-8 mg/week received an infusion of 50, 200, or 500 mg OCR or placebo on Days 1 and 15 and were observed for 24 weeks. The double-blind period was prematurely terminated because of a possible risk for serious infection from OCR. Results. A total of 152 patients were randomized into the study. The incidence of infection was 37.7% (43/114) in the OCR groups combined, compared to 18.9% (7/37) in the placebo group. Serious infections occurred in 7 patients in the OCR groups combined; there were no serious infections in the placebo group. Among the serious infections, Pneumocystis jirovecii pneumonia occurred in 2 patients in the OCR 200 mg group. The American College of Rheumatology 20% response rates at Week 24 (the primary endpoint) of the OCR 50, 200, and 500 mg groups were 54.1% (p = 0.0080), 55.6% (p = 0.0056), and 47.2% (p = 0.044), respectively, all significantly higher than that of the placebo group (25.0%). Conclusion. These results suggest inappropriate benefit-risk balance of OCR in this patient population. Because rituximab is not approved for treatment of RA in Japan, it will be necessary to investigate safety and efficacy of other anti-B cell therapies in Japanese patients with RA. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)486-495
Number of pages10
JournalJournal of Rheumatology
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 1 2012

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ocrelizumab
Methotrexate
Rheumatoid Arthritis
Placebos
Safety
Infection
Therapeutics
Pneumocystis carinii
Pneumocystis Pneumonia
Rheumatology
Cell- and Tissue-Based Therapy

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Safety and efficacy of various dosages of ocrelizumab in Japanese patients with rheumatoid arthritis with an inadequate response to methotrexate therapy : A placebo-controlled double-blind parallel-group study. / Harigai, Masayoshi; Tanaka, Yoshiya; Maisawa, Shingo; Tanimura, Kazuhide; Takahashi, Hiroki; Urata, Yukitomo; Hirabayashi, Yasuhiko; Ishii, Tomonori; Fujii, Hiroshi; Sumida, Takayuki; Terai, Chihiro; Matsumura, Ryutaro; Sueishi, Makoto; Yamamoto, Kazuhiko; Yamada, Akio; Kurosaka, Daitaro; Mimori, Akio; Miwa, Yusuke; Kuwana, Masataka; Kawai, Shinichi; Ishigatsubo, Yoshiaki; Sugimoto, Kazunori; Ogawa, Noriyoshi; Miyamoto, Toshiaki; Tamaki, Shigenori; Kai, Motokazu; Kawabata, Daisuke; Tanaka, Toshio; Inaba, Masaaki; Kumagai, Shunichi; Morinobu, Akio; Miura, Yasushi; Sano, Hajime; Kashihara, Naoki; Morita, Yoshitaka; Ezawa, Kazuhiko; Yamanishi, Yuji; Kawashima, Masanori; Yamana, Seizo; Iwahashi, Mitsuhiro; Dobashi, Hiroaki; Takasugi, Kiyoshi; Horiuchi, Takahiko; Suematsu, Eiichi; Fukuda, Takaaki; Eguchi, Katsumi; Kawakami, Atsushi.

In: Journal of Rheumatology, Vol. 39, No. 3, 01.03.2012, p. 486-495.

Research output: Contribution to journalArticle

Harigai, M, Tanaka, Y, Maisawa, S, Tanimura, K, Takahashi, H, Urata, Y, Hirabayashi, Y, Ishii, T, Fujii, H, Sumida, T, Terai, C, Matsumura, R, Sueishi, M, Yamamoto, K, Yamada, A, Kurosaka, D, Mimori, A, Miwa, Y, Kuwana, M, Kawai, S, Ishigatsubo, Y, Sugimoto, K, Ogawa, N, Miyamoto, T, Tamaki, S, Kai, M, Kawabata, D, Tanaka, T, Inaba, M, Kumagai, S, Morinobu, A, Miura, Y, Sano, H, Kashihara, N, Morita, Y, Ezawa, K, Yamanishi, Y, Kawashima, M, Yamana, S, Iwahashi, M, Dobashi, H, Takasugi, K, Horiuchi, T, Suematsu, E, Fukuda, T, Eguchi, K & Kawakami, A 2012, 'Safety and efficacy of various dosages of ocrelizumab in Japanese patients with rheumatoid arthritis with an inadequate response to methotrexate therapy: A placebo-controlled double-blind parallel-group study', Journal of Rheumatology, vol. 39, no. 3, pp. 486-495. https://doi.org/10.3899/jrheum.110994
Harigai, Masayoshi ; Tanaka, Yoshiya ; Maisawa, Shingo ; Tanimura, Kazuhide ; Takahashi, Hiroki ; Urata, Yukitomo ; Hirabayashi, Yasuhiko ; Ishii, Tomonori ; Fujii, Hiroshi ; Sumida, Takayuki ; Terai, Chihiro ; Matsumura, Ryutaro ; Sueishi, Makoto ; Yamamoto, Kazuhiko ; Yamada, Akio ; Kurosaka, Daitaro ; Mimori, Akio ; Miwa, Yusuke ; Kuwana, Masataka ; Kawai, Shinichi ; Ishigatsubo, Yoshiaki ; Sugimoto, Kazunori ; Ogawa, Noriyoshi ; Miyamoto, Toshiaki ; Tamaki, Shigenori ; Kai, Motokazu ; Kawabata, Daisuke ; Tanaka, Toshio ; Inaba, Masaaki ; Kumagai, Shunichi ; Morinobu, Akio ; Miura, Yasushi ; Sano, Hajime ; Kashihara, Naoki ; Morita, Yoshitaka ; Ezawa, Kazuhiko ; Yamanishi, Yuji ; Kawashima, Masanori ; Yamana, Seizo ; Iwahashi, Mitsuhiro ; Dobashi, Hiroaki ; Takasugi, Kiyoshi ; Horiuchi, Takahiko ; Suematsu, Eiichi ; Fukuda, Takaaki ; Eguchi, Katsumi ; Kawakami, Atsushi. / Safety and efficacy of various dosages of ocrelizumab in Japanese patients with rheumatoid arthritis with an inadequate response to methotrexate therapy : A placebo-controlled double-blind parallel-group study. In: Journal of Rheumatology. 2012 ; Vol. 39, No. 3. pp. 486-495.
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abstract = "Objective. To evaluate the safety and efficacy of ocrelizumab (OCR) in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Methods. RA patients with an inadequate response to MTX 6-8 mg/week received an infusion of 50, 200, or 500 mg OCR or placebo on Days 1 and 15 and were observed for 24 weeks. The double-blind period was prematurely terminated because of a possible risk for serious infection from OCR. Results. A total of 152 patients were randomized into the study. The incidence of infection was 37.7{\%} (43/114) in the OCR groups combined, compared to 18.9{\%} (7/37) in the placebo group. Serious infections occurred in 7 patients in the OCR groups combined; there were no serious infections in the placebo group. Among the serious infections, Pneumocystis jirovecii pneumonia occurred in 2 patients in the OCR 200 mg group. The American College of Rheumatology 20{\%} response rates at Week 24 (the primary endpoint) of the OCR 50, 200, and 500 mg groups were 54.1{\%} (p = 0.0080), 55.6{\%} (p = 0.0056), and 47.2{\%} (p = 0.044), respectively, all significantly higher than that of the placebo group (25.0{\%}). Conclusion. These results suggest inappropriate benefit-risk balance of OCR in this patient population. Because rituximab is not approved for treatment of RA in Japan, it will be necessary to investigate safety and efficacy of other anti-B cell therapies in Japanese patients with RA. The Journal of Rheumatology",
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T1 - Safety and efficacy of various dosages of ocrelizumab in Japanese patients with rheumatoid arthritis with an inadequate response to methotrexate therapy

T2 - A placebo-controlled double-blind parallel-group study

AU - Harigai, Masayoshi

AU - Tanaka, Yoshiya

AU - Maisawa, Shingo

AU - Tanimura, Kazuhide

AU - Takahashi, Hiroki

AU - Urata, Yukitomo

AU - Hirabayashi, Yasuhiko

AU - Ishii, Tomonori

AU - Fujii, Hiroshi

AU - Sumida, Takayuki

AU - Terai, Chihiro

AU - Matsumura, Ryutaro

AU - Sueishi, Makoto

AU - Yamamoto, Kazuhiko

AU - Yamada, Akio

AU - Kurosaka, Daitaro

AU - Mimori, Akio

AU - Miwa, Yusuke

AU - Kuwana, Masataka

AU - Kawai, Shinichi

AU - Ishigatsubo, Yoshiaki

AU - Sugimoto, Kazunori

AU - Ogawa, Noriyoshi

AU - Miyamoto, Toshiaki

AU - Tamaki, Shigenori

AU - Kai, Motokazu

AU - Kawabata, Daisuke

AU - Tanaka, Toshio

AU - Inaba, Masaaki

AU - Kumagai, Shunichi

AU - Morinobu, Akio

AU - Miura, Yasushi

AU - Sano, Hajime

AU - Kashihara, Naoki

AU - Morita, Yoshitaka

AU - Ezawa, Kazuhiko

AU - Yamanishi, Yuji

AU - Kawashima, Masanori

AU - Yamana, Seizo

AU - Iwahashi, Mitsuhiro

AU - Dobashi, Hiroaki

AU - Takasugi, Kiyoshi

AU - Horiuchi, Takahiko

AU - Suematsu, Eiichi

AU - Fukuda, Takaaki

AU - Eguchi, Katsumi

AU - Kawakami, Atsushi

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Objective. To evaluate the safety and efficacy of ocrelizumab (OCR) in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Methods. RA patients with an inadequate response to MTX 6-8 mg/week received an infusion of 50, 200, or 500 mg OCR or placebo on Days 1 and 15 and were observed for 24 weeks. The double-blind period was prematurely terminated because of a possible risk for serious infection from OCR. Results. A total of 152 patients were randomized into the study. The incidence of infection was 37.7% (43/114) in the OCR groups combined, compared to 18.9% (7/37) in the placebo group. Serious infections occurred in 7 patients in the OCR groups combined; there were no serious infections in the placebo group. Among the serious infections, Pneumocystis jirovecii pneumonia occurred in 2 patients in the OCR 200 mg group. The American College of Rheumatology 20% response rates at Week 24 (the primary endpoint) of the OCR 50, 200, and 500 mg groups were 54.1% (p = 0.0080), 55.6% (p = 0.0056), and 47.2% (p = 0.044), respectively, all significantly higher than that of the placebo group (25.0%). Conclusion. These results suggest inappropriate benefit-risk balance of OCR in this patient population. Because rituximab is not approved for treatment of RA in Japan, it will be necessary to investigate safety and efficacy of other anti-B cell therapies in Japanese patients with RA. The Journal of Rheumatology

AB - Objective. To evaluate the safety and efficacy of ocrelizumab (OCR) in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Methods. RA patients with an inadequate response to MTX 6-8 mg/week received an infusion of 50, 200, or 500 mg OCR or placebo on Days 1 and 15 and were observed for 24 weeks. The double-blind period was prematurely terminated because of a possible risk for serious infection from OCR. Results. A total of 152 patients were randomized into the study. The incidence of infection was 37.7% (43/114) in the OCR groups combined, compared to 18.9% (7/37) in the placebo group. Serious infections occurred in 7 patients in the OCR groups combined; there were no serious infections in the placebo group. Among the serious infections, Pneumocystis jirovecii pneumonia occurred in 2 patients in the OCR 200 mg group. The American College of Rheumatology 20% response rates at Week 24 (the primary endpoint) of the OCR 50, 200, and 500 mg groups were 54.1% (p = 0.0080), 55.6% (p = 0.0056), and 47.2% (p = 0.044), respectively, all significantly higher than that of the placebo group (25.0%). Conclusion. These results suggest inappropriate benefit-risk balance of OCR in this patient population. Because rituximab is not approved for treatment of RA in Japan, it will be necessary to investigate safety and efficacy of other anti-B cell therapies in Japanese patients with RA. The Journal of Rheumatology

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